Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

Efstathios Vassiliadis; Claudia P Oliveira; Mario R Alvares-da-Silva; Chen Zhang; Flair J Carrilho; Jose T Stefano; Fabiola Rabelo; Leila Pereira; Camila R Kappel; Kim Henriksen; Sanne Skovgård Veidal; Ben Vainer; Kevin L Duffin; Claus Christiansen; Diana J Leeming; Morten Karsdal

Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

Efstathios Vassiliadis, Claudia P Oliveira, Mario R Alvares-da-Silva, Chen Zhang, Flair J Carrilho, Jose T Stefano, Fabiola Rabelo, Leila Pereira, Camila R Kappel, Kim Henriksen, Sanne Skovgård Veidal, Ben Vainer, Kevin L Duffin, Claus Christiansen, Diana J Leeming, Morten Karsdal

Nutritional Immunology

43 Citationer (Scopus)

Abstract

Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCI₄) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCI₄-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in FO (632 ng/mL ±75, p<0.05), 54% in F1 (597 ng/mL ±41.3, p<0.05) and 62% in F2 (628 ng/mL ±59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in FO (339 ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05). Conclusion: We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.

Originalsprog	Engelsk
Tidsskrift	American Journal of Translational Research
Vol/bind	4
Udgave nummer	4
Sider (fra-til)	403-14
Antal sider	12
ISSN	1943-8141
Status	Udgivet - 2012

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Vassiliadis, E., Oliveira, C. P., Alvares-da-Silva, M. R., Zhang, C., Carrilho, F. J., Stefano, J. T., Rabelo, F., Pereira, L., Kappel, C. R., Henriksen, K., Veidal, S. S., Vainer, B., Duffin, K. L., Christiansen, C., Leeming, D. J., & Karsdal, M. (2012). Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology. American Journal of Translational Research, 4(4), 403-14.

Vassiliadis, E, Oliveira, CP, Alvares-da-Silva, MR, Zhang, C, Carrilho, FJ, Stefano, JT, Rabelo, F, Pereira, L, Kappel, CR, Henriksen, K, Veidal, SS, Vainer, B, Duffin, KL, Christiansen, C, Leeming, DJ & Karsdal, M 2012, 'Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology', American Journal of Translational Research, bind 4, nr. 4, s. 403-14.

@article{86ee378d601e44fd95c34bca94ae5374,

title = "Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology",

abstract = "Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCI4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCI4-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in FO (632 ng/mL ±75, p<0.05), 54% in F1 (597 ng/mL ±41.3, p<0.05) and 62% in F2 (628 ng/mL ±59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in FO (339 ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05). Conclusion: We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.",

author = "Efstathios Vassiliadis and Oliveira, {Claudia P} and Alvares-da-Silva, {Mario R} and Chen Zhang and Carrilho, {Flair J} and Stefano, {Jose T} and Fabiola Rabelo and Leila Pereira and Kappel, {Camila R} and Kim Henriksen and Veidal, {Sanne Skovg{\aa}rd} and Ben Vainer and Duffin, {Kevin L} and Claus Christiansen and Leeming, {Diana J} and Morten Karsdal",

year = "2012",

language = "English",

volume = "4",

pages = "403--14",

journal = "American Journal of Translational Research",

issn = "1943-8141",

publisher = "e-Century Publishing Corporation",

number = "4",

}

TY - JOUR

T1 - Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

AU - Vassiliadis, Efstathios

AU - Oliveira, Claudia P

AU - Alvares-da-Silva, Mario R

AU - Zhang, Chen

AU - Carrilho, Flair J

AU - Stefano, Jose T

AU - Rabelo, Fabiola

AU - Pereira, Leila

AU - Kappel, Camila R

AU - Henriksen, Kim

AU - Veidal, Sanne Skovgård

AU - Vainer, Ben

AU - Duffin, Kevin L

AU - Christiansen, Claus

AU - Leeming, Diana J

AU - Karsdal, Morten

PY - 2012

Y1 - 2012

N2 - Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCI4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCI4-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in FO (632 ng/mL ±75, p<0.05), 54% in F1 (597 ng/mL ±41.3, p<0.05) and 62% in F2 (628 ng/mL ±59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in FO (339 ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05). Conclusion: We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.

AB - Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCI4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCI4-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in FO (632 ng/mL ±75, p<0.05), 54% in F1 (597 ng/mL ±41.3, p<0.05) and 62% in F2 (628 ng/mL ±59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in FO (339 ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05). Conclusion: We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.

M3 - Journal article

C2 - 23145208

SN - 1943-8141

VL - 4

SP - 403

EP - 414

JO - American Journal of Translational Research

JF - American Journal of Translational Research

IS - 4

ER -

Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

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